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Like all drugs, DXM has side effects and risks. While mild in most people,
they cannot be ignored. DXM is not a "safe drug" or a "harmless drug"
(two oxymorons if there ever were). This section details side effects
that you may encounter, and is the largest section in the FAQ (other
than trip experiences).

I have reported every adverse effect (side effect) that has been related to
me as a part of a DXM experience, some that have never shown up but have
occurred with other dissociatives, and a few that are just speculation.
Many of these have been isolated events; some have occurred only when DXM
was combined with other drugs. Keep in mind when reading this section that
most, if not all, of these, are infrequent side effects. If you've ever
read the little information sheet that comes with any prescription
medicine, you'll know that pretty much any drug you take has a plethora of
side effects, most of which you'll never encounter.

I have tried to organize the side effects roughly by the frequency of
occurrence, but I have not performed any real statistical analysis yet,
so this is very rough. Instead of trying to give percentages I break
the frequency down into the following categories, with additional categories
for risks that occur with other dissociatives or may occur in theory:

Frequent

Experienced by more than 20% of DXM users

Occasional

Experienced by 5% to 20% of DXM users

Rare

Experienced by 1% to 5% of DXM users

Very Rare

Experienced by less than 1% of DXM users

Non-DXM

A known adverse effect of other dissociatives

Theoretical

A theoretical adverse effect of dissociatives

Keep in mind that I may have missed some critical research, so don't think
that just because I list a risk as "theoretical", that it can't happen to
you.

Although generally very safe, you should be aware of some of the possible
adverse effects that can occur with occasional use of DXM. These are
ordered roughly by frequency of reporting, but I don't have any
hard figures. These are all fairly minor risks or adverse effects, and
though they may contribute to a bad trip, are probably not cause for
concern. However, (and I will repeat this often), if in doubt, see a
doctor!

Probably the most commonly reported side effect is nausea, most likely
a simple result of gagging down a bottle or two of cough syrup or a
bunch of big gelcaps. People who use the gelcap or capsule preparations
do not, in general, experience as much nausea, although DXM itself, like
peyote, can occasionally cause nausea (this is less common than nausea
from syrups). DXM free base and "Agent Lemon" (see Section 11)
seem to cause the least amount of nausea.

Many cough syrup preparations can cause considerable amounts of bloating
and gas. Expect to pass gas for the next day. Stomach cramps and other
gastric disturbances, probably from the amount of sugars and thickeners,
are also common. Preparations with guaifenesin tend to induce vomiting
at recreational DXM levels. Mixing DXM with large amounts of alcohol can
have the same effect; one poor individual who mixed DXM with a large
quantity of alcohol vomited for over two hours.

Serotonin syndrome (see Section 6.2.9) is another possible
cause of nausea and diarrhea, but doesn't seem to occur
except when DXM is combined with other serotonergic drugs (mainly
antidepressants).

Closely related to nausea, DXM can cause dizziness in many users. If
you get motion sickness this is probably a bad thing; otherwise, enjoy
the free-fall sensation. Dizziness is almost certainly a result of
impaired processing of vestibular sensory input (i.e., signals from
the middle ear, where position and motion are sensed).

Ah, the "Robo Itch". Some people get it and some don't. There's evidence
that at least some of the cases of Robo Itch are a psychological reaction
to mild anesthesia, but many are probably a result of histamine release
- not necessarily an allergic reaction per se, but a possible consequence
of DXM's pharmacology. The itching tends to go away, and although
scratching is pleasurable (and a loofah is wonderful), take care not to
overdo it.

Actual allergic reactions have occurred, and often these are a result of
the "inert" ingredients, usually one of the dyes (e.g., tartrazine). A
topical antihistamine spray might be a good idea. You should always
keep an oral antihistamine on-hand, at least during your first few DXM
experiences (or when trying out new preparations). Just remember not
to use any prescription, non-drowsy antihistamine with DXM.
Diphenhydramine (BenadrylTM) is a good OTC antihistamine that is probably
safe to combine with DXM (at least it hasn't caused anyone problems yet).

People who have used CoricidinTM tablets have reported that the Robo Itch
seems to be completely absent. Be warned, however, that one should not use
DXM+antihistamine tablets above the second plateau due to the potential for
adverse anticholinergic effects (which if nothing else tend to cause bad
trips).

Note that some people find the itching to be unpleasant enough to keep them
from trying DXM again, and a few people have scratched themselves raw. Do
take care.

DXM commonly inhibits orgasm in males and occasionally in females. When
orgasm does occur it is often accompanied by profuse sweating and muscle
rigidity. Sex probably isn't a good idea due to the potential for aggravating
hypertension (see Section 6.1.12). Besides, the inhibiton of tactile
sense tends to make sex a less than thrilling experience.

Many DXM users note sweating both while on DXM and for several hours after
coming down. Some have noted a peculiar odor to the sweat, which may be
metabolites of DXM or may simply be a consequence of enhanced sense of
smell. In any case, just drink lots of water and you should be fine.

This one's a no-brainer. DXM inhibits normal mental functioning. That's
why people take it. Whether this is fun to you is, of course, entirely
up to you. Some people simply find DXM makes them feel too stupid.
There is also some evidence for impairment of judgement, so a trip sitter
is a good idea. Oh, and don't think for a moment that you can drive on
DXM; even if you can't tell, it greatly reduces reaction time.

This seems to be fairly common but not particularly serious; generally,
a heart rate in the range of 90 to 120 can occur. This is probably
a side effect of the stimulant qualities of DXM. Substantially
higher heart rate may indicate a panic attack (see Section 6.2.1).

Two users have reported that benzodiazepines (esp. clonazepam) prevent
this side effect.

Although it doesn't happen to everyone, some report substantial
pupil dilation on DXM, similar to the pupil dilating effect of LSD.
This is probably a dead giveaway that you're "on something",
so you might want to know if it happens to you before trying to
get away with being on DXM in public. And may your eyes dilate to
the size of saucers and attract cops for miles around if you ever
drive on DXM!

There are also a limited number of reports of pupil constriction.
These seem to occur with much less frequency. In both cases,
pupils remain normally responsive to light. Two people have
reported to me that their pupils were significantly different
in size; usually this is an indication of something Very Wrong
going on in the brain (hemorrhage, stroke, or other CVA), so if
this happens to you, seek medical assistance! It is possible that
this may occur as a result of asymmetrical effects of dissociatives
on the cerebral cortex, and isn't indicative of any damage at all.

Hot and cold flashes during the trip occasionally occur, and are
not generally serious. One user reported frequent extreme hot
flashes, which eventually got bad enough that he sought medical
assistance. A few people have reported hot flashes several days
after the DXM trip is over. This may simply be a phenomenon of
sensory dissociation, or it may be indicative of an actual
fluctuation in core temperature (see Section 6.1.13).

A few have reported that eating a small amount of food from time to
time can prevent hot and cold flashes, so they may be related to
rise and fall in blood glucose levels.

Two users have reported that benzodiazepines (esp. clonazepam) prevent
this side effect.

DXM, like other dissociatives, can cause mild hypertension (high blood
pressure). This is not generally considered serious, as the elevated blood
pressure is still within the normal range. If you have high blood pressure
to begin with, stay away from DXM (or stimulants for that matter).
There are cases of serious hypertension from dissociatives; see
Section 6.2.6.

Two users have reported that benzodiazepines (esp. clonazepam) prevent
this side effect.

A rise in body temperature of about 1 degree Farenheit (0.5 C) has been
noted by many users of DXM, and low-grade fever is one of the hallmarks of
dissociative intoxication. It doesn't seem to be a serious condition.
Serious rises in body temperature have been noted with dissociatives,
however; see Section 6.2.5.

Two users have reported that benzodiazepines (esp. clonazepam) prevent
this side effect.

As DXM is a dissociative anesthetic, it will make you less aware of the
normal body senses, including muscle fatigue and pain. As a result you can
easily over-exert or over-stretch yourself, especially if you are out dancing
or engaging in other physical activity. Pay close attention to your body if
you plan on moving a lot.

On a somewhat related note, many people report that heavy exercise under the
influence of DXM can cause nausea. This seems to occur mainly at the second
plateau and above; in contrast, one user reported swimming on a first plateau
dose to be a very pleasant experience.

Urticaria, a skin rash or wheal typically consisting of white or red
bumps, is rarely reported from DXM, and typically appears on the arms or
less commonly the chest or face. It is probably related to histamine
release. It goes away soon after the trip is over.

Two people have reported greatly increased bile secretion from DXM. It's
possible that DXM may be released into the bile and may be subject to re-
absorption, but this has never been demonstrated. In any case, although
this may be a source of discomfort, it doesn't seem particularly serious.

Some people have reported slightly to moderately inappropriate behaviour
while on DXM. The most common example of this is blurting out whatever
comes to mind, i.e., avoiding those little white lies we normally hold on
to for the sake of politeness. Other cases included public nudity, impaired
grooming, and abnormal gestures.

There are numerous examples in the literature of inappropriate (and often
dangerous) behaviour in PCP users, but to my knowledge nobody has yet done
anything terribly outrageous or dangerous while on DXM.

One user with a blind spot in one eye due to a stroke reported hallucinations
in the blind spot persisting for several days. This eventually went away
but was not particularly enjoyable. LSD, cannabis, and alcohol all failed to
induce this effect. Ketamine did, however. DXM may also interfere with the
biological clock and prevent light entrainment (221,230).

There are also more serious adverse effects that can occur from DXM use.
All of these should be taken seriously, and if at all in doubt about your
health, see a physician immediately. As far as I know nobody has ever died
or suffered serious injury from any of these adverse effects, but they
generally aren't pleasant either.

Several users have reported panic attacks, and I am beginning to think some
people may be susceptible to this from DXM. This seems to be worse when
DXM is combined with other drugs, including marijuana (cannabis). The
trouble with a panic attack is, once you realize you're having one, it
can make you feel out of control of the drug experience, which makes the
panic attack even worse. This is a difficult vicious circle for some
people to break. Fortunately this mostly seems to happen with high doses
(around 10 mg/kg and up).

If you find yourself having a panic attack, there isn't really much that
you can do for yourself except relax, take deep and even breaths, and try
to calm down. If you find yourself hyperventilating, breathe into a
paper bag (which really does work, by raising blood CO2 levels).

Benzodiazepines (ValiumTM and related drugs) are an effective treatment
for panic attacks. However, they have several drawbacks. They must be
prescribed by a physician (at least in the US), and they will usually
stop the DXM experience very suddenly. They are both psychologically
and physically addictive, and withdrawal from regular use can cause brain
damage.

Benzodiazepines, esp. clonazepam, may prevent panic attacks from DXM,
but must be used with care and under the guidance of a physician.

Psychological side effects to psychedelics can be quite varied. Bad
trips are certainly possible, as with any drug. As with other psychoactive
drugs, especially hallucinogens, there is always the chance that a mental
illness may be triggered by the experience. Keep in mind that DXM is
related to PCP, and some people really don't get
along well with dissociative anesthetics. The chance of experiencing a
psychotic episode probably increases with dosage.

Many of the cases of DXM "abuse" in literature have concerned psychotic
episodes (the same is true for LSD). This probably skews the perception
of how frequent these events are, since most of the published accounts
come from hospital visits. The vast majority of DXM users do not experience
psychotic breaks. From personal communications I have noted nine cases of
DXM-induced psychotic breaks that required hospitalization; of these, six
involved regular users.

I've already mentioned how DXM impairs driving ability. It also seems to
impair judgement, both about one's abilities and one's susceptibility to
harm. This is bad news when it comes to driving and other critical
situations. So before you consider doing anything where your life may
be on the line, know good and well that DXM will impair your
performance.

Disturbingly, DXM also impairs judgement in sexual behaviour. While it
does tend to make orgasm difficult for males, it has also been known to
impair good judgement about sex. While I don't think DXM has the same
ugly potential as Rohypnol or other benzodiazepines, it can make you
stupid and fearless enough to not use protection, and that can be a
deadly mistake.

I have actually heard from one person about DXM being used to lower
inhibitions for the sake of getting someone's consent. This is an
entirely detestable practice, although not limited to DXM (alcohol is
used regularly for this purpose daily, but that doesn't make it right).

Let me put it simply. If you and your partner want to use DXM with the
intention of having sex on it, that's your business. But if you use DXM
to lower someone's inhibitions, that's an entirely different situation.
Basically, it means you can't get laid without impairing someone's
judgement. There's a word for that: loser. It'll also get you
thrown in prison, where you can find out how much fun nonconsensual sex
really is.

Besides, it's much more fun where the other person has all their
mental and physical abilities.

One person reported a long-lasting depression and paranoia after a single
episode of DXM use. This individual was age 15 at the time; I suspect
that young teens may be more susceptible to depression and other mental
illnesses from DXM use than adults.

One user reported a case of hyperthermia (increased body temperature)
which could have been dangerous, with a rise in body temperature
to 103 F (38 C). The individual in question also had a cold at the
time, so part of this might have been a result of existing illness.

In the case of serious hyperthermia there is an immediate need to
lower body temperature. Sponge baths with cool water and drinking cold
liquids are the safest way, although a few physicians have recommended
ice-water baths for severe cases. ALWAYS have someone sober to make
sure the person doesn't go into shock and drown. Whenever body
temperature nears 105 F (40 C) you should get medical attention.
Temperatures at or above 107 F (41 C) will probably cause permanent
brain damage.

There is a condition that occurs sometimes with volatile anaesthetics
called Malignant Hyperthermia, which is often fatal and seems to
involve genetic susceptibility. Malignant Hyperthermia can raise temperature
to 112 F (44 C) and is obviously a different sort of threat than the one or
two degree temperature rise from dissociatives. I have never heard of it
occurring with any dissociative (anaesthetic use or not).

I have heard of only one serious case of hypertension, when DXM was
used in combination with pseudoephedrine. DXM itself typically raises
blood pressure slightly (although a few people experience a drop in
blood pressure). This is probably due to sympathetic activation from
DXM's dopamine reuptake inhibiton and from downstream effects of NMDA
blockade.

Take care combining DXM with stimulants or physical exertion. There
is always a chance of hypertensive crisis and hemorrhage, and it's
not always easy to predict. If in doubt consult a physician, since
drugs which lower blood pressure aren't commonly available, and must
be used with considerable care. Avoid DXM if you have an existing
high blood pressure condition.

PCP use has been cited as a cause of rhabdomyolysis, a condition where
muscle cells break down, and myoglobin and other bits and pieces of muscle
cells leak out into the bloodstream. To put it simply, they don't belong
there, and the body doesn't know what do with them. They end up essentially
clogging the kidneys, which shut down. This can also occur with a variety
of stimulant drugs, including amphetamine and MDMA (ecstasy).
Nobody's really quite sure why this happens, although some believe it to be
a combination of repeated or excessive muscle cell activation, dehydration,
and high body temperature (not surprisingly, most MDMA-induced rhabdomyolysis
takes place at raves).

This is of course a serious condition, but hasn't to my knowledge ever
occurred from DXM. It's not always fatal, but if enough muscle tissue
is destroyed, it can be. Needless to say, medical intervention is
required.

I have received anecdotal evidence from one person who complained of
prolonged illness (3-4 days) following DXM use, during which she did not
produce urine, followed by about three hours of bloody urine. Needless to
say she didn't repeat the experience. I haven't a clue if this could have
been rhabdomyolysis (and she didn't consult a physician at the time), but
obviously something was amiss with the kidneys. Incidentally, this occurred
after years of DXM use.

One of the risks of high doses of dissociatives, and in fact the proposed
mechanism for overdose fatalities, is respiratory depression (201). The two
medically recorded deaths due to DXM overdose (one of which was a suicide)
were attributed to this. I have never heard of any other cases of
DXM-induced respiratory depression, although I suspect it is a serious
threat at doses above 15 mg/kg.

The real danger of respiratory depression (other than death of course)
is hypoxia (insufficient oxygen) and subsequent brain damage. DXM does,
of course, protect the brain from hypoxic damage, so hypoxia with DXM
is probably safer than an equivalent degree of hypoxia with opiates,
but there's still no need to put your brain at risk. In the grand scheme
of things hypoxia is just one risk among many for brain damage with regular
use of high-dose DXM, but the actual data from DXM users shows that brain
damage is extremely rare.

A lot of people worry about respiratory depression because of a feeling of
shortness of breath that often accompanies DXM intoxication. This may be
a consequence of the brain "taking over" breathing from conscious control,
as well as impaired perception of the breathing process. If you're really
worried, stop taking DXM. I suppose you could rig up an oxygen mask, but
if you're enough of a hardcore psychonaut to consider that you probably
don't need my help.

Serotonin syndrome is a recently-identified condition that typically occurs
when combining serotonergic drugs (i.e., drugs that stimulate, or mimic,
serotonin activity in the brain). Most of these drugs are antidepressants
(MAOIs, SSRIs such as ProzacTM or ZoloftTM, tricyclics, lithium, and
atypical antidepressants); others include buspirone (BuSparTM), MDMA
(ecstasy) and other phenethylamines, tryptophan, harmine and harmaline
(both recreational MAOIs), and possibly serotonergic hallucinogens such
as LSD, psilocybin, and DMT. Phentermine, fenfulramine, and phen-fen
can also cause serotonin syndrome when combined with DXM.

DXM induces a release of serotonin, and while it has never been
demonstrated to cause serotonin syndrome by itself, it has been shown to do
so in combination with other serotonergics (365). In particular,
combining SSRIs and DXM may be risky; one paper found serotonin syndrome
from an SSRI combined with DXM with a concurrent vascular disease (364).

Serotonin syndrome is indicated by a combination of three sets of symptoms:
changes in mental status, autonomic dysfunction, and neuromuscular
abnormalities. Specific symptoms include:

Changes in Mental Status

hypomania

confusion

agitation

Autonomic Dysfunction

diarrhea

low-grade fever

diaphoresis (sweating)

shivering

Neuromuscular Abnormalities

myoclonus (sudden, brief muscle spasms)

hyperreflexia (exagerrated reflexes)

ataxia (incoordination and clumsiness)

Yes, there is some overlap (e.g., shivering can considered as an autonomic
dysfunction or a neuromuscular abnormality).

Treatment of serotonin syndrome requires medical intervention, and consists
of supporting measures to treat the symptoms, and possibly antiserotonergic
drugs. Benzodiazepines (such as ValiumTM) have also been used with
considerable success (366).

The astute among you will notice that many of these "symptoms" are
characteristics of DXM intoxication. In fact, many serotonergic drugs can
cause these symptoms. The question is whether or not the symptoms become
severe and numerous. At least one symptom from each of the three categories
is generally required for a diagnosis of serotonin syndrome.

Once again, if in doubt, see a doctor. And avoid using DXM in combination
with any antidepressant. Remember, combining DXM with a MAOI has been
repeatedly fatal!

It is possible to have a major allergic reaction to DXM or to one of the inert
ingredients (typically tartrazine). An antihistamine is the obvious solution.
If you are allergic to aspirin you may be allergic to tartrazine, and in any
case it is a good idea to try DXM at a very low dosage first to rule out
allergic reactions to any of the ingredients found in cough syrups. You should
also repeat the low-dose test every time you try a new syrup, gelcap, or other
DXM formulation.

I have never heard of a serious case of DXM-induced histamine release but it is
a possibility. Again, an antihistamine should help, but if things continue to
get worse, get medical help.

Even though DXM has been successfully used to prevent seizures,
it may actually induce them at high dosage levels (45),
especially in epileptics (142). You want to avoid this.

Some users who have taken very high dosages of DXM (above 15 mg/kg) in
products containing guaifenesin have lost motor function to the point
of choking on their tongues (or at least feeling like it; I've been told
that this is technically impossible but I've also been told it isn't).
Obviously, nobody should be experimenting at this level without a (sober)
assistant. If this happens, seek medical assistance. While I cannot vouch
for the efficacy or safety of this procedure, I have been told that one can
maintain the airway by grabbing the person's tongue and holding it out of
his or her mouth until motor function is regained (or the ambulance comes).
Don't try to insert anything into the person's mouth; it could slip and make
the problem worse.

Prolonged, regular use of DXM has some definite risks. Generally speaking
the most common is mania, which has been reported in people using large
amounts of DXM (especially to self-medicate depression) (1-3,132,136,139-141).
This is probably a combined effect of dopamine reuptake inhibiton, downstream
effects of NMDA blockade, and possibly sigma receptors (see Section 10).
One user who had formerly used the antidepressant bupropion (WellbutrinTM)
reported a similar but somewhat stronger antidepressant effect from DXM,
though with greater adverse side effects.

This section may also apply in the case of drug "binges" (using DXM
continuously of more than one day). This is to my knowledge much more
common with other drugs than DXM, since it does tend to induce a fairly
significant hangover after awhile (if for no other reason than the cough
syrup is hard on your stomach).

The most serious adverse effects are all related to brain damage. This
is a well documented risk of PCP in humans and has been shown with all
dissociatives in animal models! The good news is this doesn't happen
at human recreational dosage; the bad news is the animal models may not
predict the effects of regular use at lower dosages. The other bad news
is that PCP may induce brain damage by other mechanisms; the other good news
is PCP is unlike DXM or ketamine, and neither DXM or ketamine users have
shown much impairment.

This time I have tried to organize by categories representing the degree of
seriousness of the adverse effects: permanent brain damage, physical toxicity,
temporary mental impairment, psychological disorders, and miscellaneous.

Onley's Lesions (named after a researcher named Olney, appropriately enough)
are a particular type of damage observed from NMDA antagonists (dissociatives).
Damage occurs primarily to the posterior cingulate and retrosplenial cortex
(289), and to a lesser extent the entorhinal cortex, dentate gyrus, and olfactory
regions (213). The posterior
cingulate may be involved in evaluating one's own behaviour (316), verbal and
auditory memory (294), spatial memory and cognition (316), and language,
notably metaphor comprehension (303). The retrosplenial cortex may be involved
in novelty encoding (321) and learning, memory, and emotional behaviour (324).
The hippocampus and adjacent areas are well known to be deeply involved in
intermediate-term memory and forming relationships between sensory data, and
damage to the hippocampal formation causes amnesia both in humans and animals.
Full detail on Olney's lesions is given below; see Section 6.5

If this strikes you as areas that DXM interferes with, congratulations,
you've been paying attention. On the other hand, these are functions that,
according to all human research, recovers after occasional use of
dissociatives. There is considerable documentation
of PCP users suffering deficits in language (especially finding words),
memory, cognitive skills, and motor skills (which may be a result of PCP's
peculiar toxic effects on the cerebellum not shared by other dissociatives).
Perhaps most disturbingly, this damage also includes the ability
to form emotional ties and recognize emotions in others, and an increase in
flattened affect (outward emotionality). PCP's reputation for creating
psychopaths is probably 99% media hype, but in this case (unlike most
drugs the media demonizes) it probably has a kernel of truth.

PC has been well studied, and an on-line review is available (355). Some
of the papers cited in this source are, in my opinion, a bit dated, but
it provides a good starting point for understanding what can occur with
long-term high-dosage use of dissociatives. Some speculate
the damage is caused by hypertensive strokes or hemorrhages, although it is
worth noting that this speculation was made prior to the knowledge of Olney's
lesions.

Studies with PCP show that this sort of damage sometimes does
resolve (though sometimes after months or years). And
users of ketamine seem to show considerably less damage than users of
equivalent amounts of PCP (pers. comm.). Even more skepticism is warranted
since one popular method for making PCP involves a precursor chemical which,
when heated, releases cyanide gas (196). Samples of street-grade PCP show that
many contain a fair amount of this precursor (the sloppiness of drug chemists
is probably the biggest reason to avoid synthetic drugs).

Still, I have received a few anecdotal reports of DXM-induced
degradation of mental performance that are consistent with this type of
damage. To be precise, I have received eight first-hand reports of this over
the past five years, and have read about one other. Three of the eight
seemed to show permanent damage; in the other five, it resolved after
several months and may have been due to depression. There have been
numerous second-hand stories ("I heard from this ex-girlfriend about this
guy who drank a bottle of cough syrup and his brain melted and ran out his
nose"), but I don't necessarily consider them accurate.

The published account (136) involved a 39-year-old insurance salesman
who consumed 1500 mg DXM, 5000 mg guaifenesin, and 3 mg alcohol, about once
per week. A SPECT scan showed widespread dysfunction of the cerebral
hemispheres, and EEG mapping showed excessive right central alpha activity.
The researchers suggested a concurrent diagnosis of temporal lobe epilepsy
on the basis of extreme religiosity andexcessive note-writing (although I've
known more than one who experienced this from DXM). His condition continued
to deteriorate after ceasing DXM use.

One former user told me of his experiences following use of 720 mg
DXM twice to three times a week for 3 months, and then four to five times
a week for another three months. After quitting DXM, he experienced
uncontrolled shaking of muscles and severe muscle fatigue for three years,
and permanent difficulties in forming complex thoughts into words. He
described the latter as "trying to make a complicated sentence out of
alphabet soup".

Of the first-hand accounts, three involved concurrent use of other drugs,
in all cases stimulants (pseudoephedrine in one, amphetamines in the other
two), and in one case (DXM and amphetamine) also PCP, ketamine, and MDMA.
Of the four cases not involving other drugs, all four used in excess of
1000 mg per week, three using over 2000 mg per week, and all four for a
period of at least six months.

To make matters even more complicated, I've also spoken to at least twelve
other people who have used in excess of 1000 mg per week for a period of one
year or more, without obvious evidence of lasting impairment. One was
formally tested and showed no significant impairment. A few of them remarked
that there was a recovery period of several months to two years during which
they felt "burned out".

So how do you avoid this sort of damage? Well, the obvious way is, don't
do DXM. However, people regularly use drugs which can and often do cause
brain damage (including alcohol, cocaine, amphetamines, and depressants),
so I have a sneaking suspicion not everyone is going to drop that bottle
of Tussin and walk away from the medicine cabinet.

The best advice I can give you, other than Just Say No, is Just Stay Low.
Keep doses as low as necessary to meet your objectives, using meditation,
sensory deprivation, theta stimulation, etc., to boost the effects (see
Section 7.4). And since I mentioned it, don't
use DXM without a set objective and goal. It is not a casual
psychedelic which should be taken just to relieve boredom; that's why the
Goddess gave is marijuana and mushrooms (wait, I can't say that ... strike
that.) Okay, fly to somewhere where it's legal and then
smoke marijuana. Don't break the law. But more importantly, don't use
DXM so often that it becomes damaging. Besides, like any other psychedelic
it loses its magick when used too often.

If you have already spent the last five years drinking gallons of cough
syrup, maybe now is the time to stop, wait a year or so, and then decide
whether you want to continue. More practical advice for psychonauts and
the hardcore is given below, in Section 6.5.

PCP has been repeatedly blamed for causing cerebro-vascular accidents
(CVAs) such as hemorrhages and strokes, with numerous papers referring
to this (a good review is provided in (355)). In conversation
(pers. comm.) and "off the record" one researcher into dissociative
neurotoxicity told me that this mechanism may be
less established than it seemed, for the following reasons:

Most of the research suggesting CVA damage from PCP
came out during the initial PCP epidemic,
when it was obvious that people were being hurt but there wasn't
much time to figure out why, and the research was somewhat
rushed.

Nobody at the time knew any mechanism for NMDA antagonist
neurotoxicity and it wasn't considered as a possible culprit.

Many people who used PCP were polydrug abusers and mixed it
with amphetamines, cocaine, or other stimulants, a practice
which is much more likely to result in hypertensive CVAs

Much of this research was funded during the early years of the
War on Drugs, and other research from this time is known to
be biased.

Still, the concensus among everyone (this researcher included) is that
PCP, especially street-grade, is bad stuff, and while one hit isn't
likely to fry your brain, continued use might. Whether this is due to
Olney's lesions or CVAs is to some degree a moot point.

The symptoms of a CVA can include sudden (often intense) headaches,
slurred speech, ataxia, confusion, numbness or loss of muscle control
to parts of the body, and abnormal pupil responses. That some of these
are also symptoms of DXM intoxication complicates matters for physicians,
so make sure if you do see a doctor you tell her or him about your DXM
use (and what it does).

There is, I think, enough data to show that PCP is possible of inducing
CVAs, at least in those with underlying hypertension and who go on
"binges". It's never been demonstrated with DXM, but there hasn't
been nearly as much use of DXM as PCP either. Perhaps with increasing
recreational use of ketamine the issue will be resolved. If you use
any drug regularly you should seriously consider donating your body to
science when you die, since it really will help us in our understanding
of the actual dangers of drugs. Not that a solid knowledge of the
dangers of alcohol and tobacco stop anyone from using them, mind you.

I know of one person who developed a severe headache during an extended
DXM trip, which lasted for several days. This person experienced no loss
of mental ability, but hasn't had an MRI (a type of brain scan) either (and
isn't likely to since they don't come cheap). So who knows, it could have
happened. If it makes you any happier, a DXM-induced CVA is probably
healthier than one induced by stimulants, since the secondary quinolinic
acid induced damage (see Section 4.15.2) is blocked
by DXM. Still, that's small comfort when you risk irreversible brain damage.

Some have suggested that chronic NMDA blockade may be a mechanism for
Alzheimer's disease (100), though this could be due to advanced stages of
Olney's lesions. There is also a remote possibility of toxicity to
5HT (serotonin) neurons due to induced overactivity, similar to that
resulting from MDMA (52). This has, however, never been observed with
any dissociative.

Excitotoxic rebound is a process by which brain cells, accustomed
to a lower level of activity, essentially "burn themselves
out" when a depressant drug is removed. Alcohol, benzodiazepines
(tranquilizers, e.g., ValiumTM), and barbiturates (sedative-hypnotics
or "downers") are well known for causing severe excitotoxic
rebound. It is possible that regular use of DXM could lead to
an upregulation (i.e., increase in number) of NMDA receptors as
the body tries to compensate for the blocking effect of DXM. Recent
research suggests that NMDA receptors do not upregulate with blockade,
so excitotoxic rebound probably isn't a major factor to worry
about.

As stated above, mania has been documented from regular use of DXM
(1-3,132,136,139-141). There may be biological susceptibility to it.
One of the problems with mania is that, unlike depression, manic patients
are often unaware that they are suffering from a psychological disorder.
In all recorded cases, mania went away when DXM use was discontinued.

In addition to mania, DXM can also induce depression, although
depression is more often associated with DXM withdrawal. In a few cases,
depression can occur even during DXM intoxication. This can range from
mild dysphoria to suicide attempts, and there have been a few anecdotal
reports (unverified, at least by me) of actual suicides among heavy DXM
users. These stories were one of the reasons that one group of DXM users
discontinued using DXM. There is also a published case of a successful
suicide attempt by DXM, although it is not known if DXM-induced depression
had anything to do with it.

There is some research right now indicating that dissociatives may actually
have antidepressant effects (208,212,223,245,250), but other research casts
doubt on this (225,229). It seems that in animal models, dissociatives can
act like
antidepressants on some tests, but not necessarily others. What may be
happening is that, by inhibiting memory and overall cognitive function, the
dissociative is producing identical results in the test models but for a
completely different reason. Others suggest that dissociative depression
occurs primarily when tolerance is reached and as a result of withdrawal,
or because of a perception of significant mental impairment and the fear
that it might be permanent. Withdrawal does improve cognitive
abilities (355).

Whatever the reason, it does seem to be a real risk of long-term use. If
you start finding yourself hostile or depressed, or your friends start
mentioning it, lay off the DXM for a few months and see a mental health
professional.

A few regular users of DXM have reported to me that, after a year or so of
constant use, they developed regular, violent ideations, and would tend to
respond in anger to any perceived threat. A few others have noticed a
paranoia while using DXM regularly. Two may have exhibited antisocial
behaviour but to my knowledge no formal tests have been done (and in one
of these cases I suspect the individual wasn't terribly social to begin
with).

My hunch is DXM may actually be more pleasant to antisocial personalities
because it seems to impair perception of social cues, reduce stress
related to social situations, and generally reduce inhibitions. It may
be that antisocial personalities just happen to like DXM more than others,
who don't enjoy being cut off from interpersonal interactions and social
behaviour (or who find such interaction to be more unpleasant than most).

It is possible that violent ideations coupled with psychotic breaks could
result in violent behaviour; this is a well known side effect of PCP,
and can have such extreme consequences as parents trying to kill their
children (199). However, these cases are not nearly so common as they are
made out to be (192).
Also, one paper on PCP found that violence was correlated with personality
and background, and not everyone was susceptible (193).

The only person who reported this with whom I've communicated after he
stopped using DXM told me that these symptoms went away after about three
months.

DXM inhibits memory. If you use it regularly, your memory will be
impaired. No big secret here; if you smoke weed all the time you probably
won't have much of an attention span either. Still, don't forget that
it can take awhile (up to a month or so) for memory to come back to normal
after discontinuing DXM. And since DXM inhibits encoding of memories,
keep in mind that you may not have coherent memories from times when you
used DXM, even for days after the experience. This is nothing new to
alcoholics, of course, but it isn't exactly fun in either case, and years
from now you may find yourself regretting not having remembered the times
when you regularly used DXM.

While on high doses of DXM most people remark on impaired language
skills, especially being unable to find the correct word. With regular
use of DXM, many people have noticed that their "inner narratives" become
more and more abstract and pre-linguistic, and that they find it more and
more difficult to convert concepts into language. Some of this may be
due to the fact that the mental states induced by DXM don't really have
terms, but I have little doubt that there is some transient (and possibly
permanent) inhibition of language skills. Although in all cases I've
known of (except for those listed above under Section 6.3.1)
this has been a temporary phenomenon, it's possible that language skills have
to be re-acquired after loss of brain cells. Unproven, but possible.

One person remarked that it felt as if the skills had been somewhat
forgotten due to lack of use, since DXM tended to make him think in terms
of pure concepts rather than language, and that as soon as he started using
language in his inner narratives, the skills came back. Perhaps like
muscles, mental skills must be used regularly to stay in shape.

Before you get any stupid ideas, the weight comes back after you stop using
DXM and typically you end up worse off than before (similar to speed in
this respect). I wouldn't mention it, but I've spoken with someone who used
heroin for the weight loss (somehow I think this person's going to get the
Darwin Award). Now that I've hopefully dissuaded everyone, here's the skinny
(so to speak). Regular use of DXM can induce weight loss, typically about 10
to 20 pounds (4.5 to 9 kg), and although I don't know how much is fat and
how much muscle, I suspect it's not all fat, since one regular user noted
a significant decrease in strength.

Part of this weight loss is probably due to a drop in appetite, since it
inhibits appetite for food (as well as most other physical appetites) and
since one is often nauseous from drinking cough syrup. Part of it may be
due to a stimulant effect, or an increase in metabolic rate. Regardless
of the reason, it is temporary.

At high enough doses, DXM, like any other dissociative, can cause loss of
muscle control, but that's not what I'm referring to. With regular use
of DXM, some people have noticed extreme weakness and muscle tremor, like
that found during exhaustion with weightlifting. Exactly is going on is
beyond my knowledge; it may be related to blood glucose (everyone who
mentioned this was a regular user of cough syrup), it may be neuromuscular
in nature, or it may be a result of exhaustion from muscle rigidity.

It's worth noting that DXM (more so than DXO) blocks calcium channels, and
that regular use of DXM may lead to a buildup of DXM in the bloodstream
which could eventually affect calcium channels. This is idle speculation,
however. Regardless of the cause, this sort of problem is probably your
body's way of telling you to lay off the drugs.

Anything can become psychologically addictive: drugs, television, shopping,
gambling, sex, masturbation, thumb-sucking, whatever. Generally speaking
though one can distinguish a point at which one's habits become self-
destructive, and at this point it's generally safe to say psychological
addiction has occurred.

There is much talk when discussing any drug about the difference between
psychological and physical addictions. At the extremes, this isn't so
difficult to understand. Rats won't self-administer LSD, and people who
take LSD compulsively are psychologically addicted. People who use
alcohol regularly eventually require alcohol for their brains to function
normally, and are considered to be physically addicted.

In the middle is a grey area. Is caffeine physically addictive? With
regular use, the brain does adjust to it, and there is a well-defined set
of withdrawal symptoms, but people don't generally think of caffeine as
being physically addictive. The same holds true for nicotine, which
some rate as the most addictive drug known to man.

More recently, psychological addiction has come to be understood as the
desire or need to take a drug (especially when there are serious
consequences to doing so), whether out of enjoyment of the drug (primary
psychological addiction) or out of a desire to avoid the negative effects
of withdrawal (secondary psychological addiction).

There are documented accounts of DXM users who continued to use DXM in spite
of adverse consequences (136), and I have received about two dozen
reports of people whose use of DXM caused them significant trouble. Everyone
I was able to follow up on had discontinued use, although some experienced
relapses into use. This follows the patterns of PCP users (195,202-203).

Based on this I would say that DXM is habit-forming or psychologically
addictive. How much? Well, it's hard to tell; any rating of addictiveness
is definitely subject to bias. Personally, I'd say it's more addictive
than marijuana, and probably about as addictive as (or slightly less than)
alcohol, in those susceptible to dissociative addiction. There does seem
to be some sort of factor (or factors) which are involved, since many people
can use large amounts of DXM without ever developing a habit. Whether these
factors are a part of personality or biology is beyond my knowledge.

Psychological addiction is not itself a threat, although there can be
economic and social consequences to it. After all, not everyone likes
being around someone who is high all the time, and it does impair your
ability to hold down a job, go to school, and interact with your loved
ones when used to excess. More importantly, however, regular DXM use
may bring about long-lasting or even permanent mental impairment.

Tolerance and physical addiction are two different things, although some
would argue that the first is a necessary condition for the second. Tolerance
occurs where increasing doses of a drug are required to maintain a given level
of a drug's effect. One can become tolerant to many drugs, whether they
affect the mind or not; some examples are caffeine, alcohol, stimulants,
depressants, opiates, nicotine, nasal decongestant sprays, and aspirin and
related NSAIDs.

Physical addiction is generally viewed as a condition where the drug is
needed for normal function of the body or brain. Tolerance to the effects
of drugs can occur without physical addiction, e.g., when tolerance occurs
as the body becomes more effecient at metabolizing the drug. However, in
the case of psychoactive drugs, tolerance and physical addiction usually go
hand in hand.

The big exception to this is the psychedelics. Any LSD user will tell you
that tolerance to LSD builds quickly; however, there doesn't seem to be any
"LSD withdrawal" when one stops using it that requires one to take LSD to
maintain normal function. Though I had formerly worried about rebound
excitotoxicity at NMDA receptors, it seems that NDMA receptors do not
upregulate with use of DXM; it also doesn't appear that dissociatives
are physically addictive (194). They do induce tolerance, some would
argue extremely rapid tolerance (called tachyphylaxis), since a second dose of
a dissociative a few hours after coming down off the first doesn't seem
to induce the same level of effects. This may be related to alcohol
tachyphylaxis, since many of the behavioural effects of alcohol may be
a result of (direct or indirect) NMDA blockade.

To sum it up, DXM does seem to induce tolerance (and I would guess it is
cross-tolerant with PCP and ketamine, but nobody's ever tested that), but
there does not seem to be an appreciable withdrawal symptom beyond drug
craving (194). Some might disagree, pointing out a definite set of withdrawal
symptoms from dissociatives including restlessness, dysphoria, depression,
and flattened affect, but these may just be an effect of long-term
use itself that persists for some time after discontinuing the drug.

DXM, like other psychedelics (and for that matter any intense experience)
can induce psychotic breaks which can be long-lasting. Personal
susceptibility seems to be involved here, and some people may have latent
mental problems which are triggered by DXM. I definitely would advise
against DXM use if you have a history or family history of mental illness,
especially schizophrenia, depressive disorders, or antisocial personality
traits.

The threat for this sort of thing goes up as use becomes more regular, and
some have noted that DXM made them a little bit crazy when they were using
it regularly. One person with whom I spoke didn't think this was such a
bad thing, but none of the others enjoyed it much. This isn't a particularly
common problem, but shouldn't be ignored either. You never know if you're
susceptible to a psychotic break until you have one, and coming to your senses
in a padded room probably isn't the best trip in the world. Treatment includes
antipsychotic drugs and in rare cases electroshock (200).

Some research has linked sigma receptors to schizophrenia (46-49),
and chronic use of NMDA antagonists has been shown to upregulate (increase
the number or activity of) dopamine receptors (50). This could
theoretically mean that DXM could trigger schizophrenia or mania in
susceptible individuals. Some researchers have suggested that chronic
NMDA blockade and/or sigma activity may be responsible for schizophrenia
(100).

I have found no evidence of damage to the liver, kidney, or pancreas from
DXM in medical research, however, there are potential mechanisms for it.
DXM itself is metabolized fairly easily; it's the inactive ingredients
and some of the more unlikely side effects one has to worry about.

Drinking cough syrup dumps glucose into your bloodstream, and doing this
repeatedly on an empty stomach probably puts a load on your pancreas (and
stomach, adrenal glands, and probably other parts of your body as well).
True, that's their job, but one can overwork any organ. A few long-term
users of DXM have reported that after years of use they became intolerant
to any amount of sugar on an empty stomach.

There's also the possibility of damage to the liver, especially if the
enzymes inhibited by DXM (cytochromes P450-2D6, 3A4, and 3A5) are also
involved in metabolizing something else, and that something else ends up
being metabolized by another enzyme into something dangerous. This is
the sort of thing one has to worry about when inhibiting liver enzymes,
and it does occasionally cause problems; as an example, DXM will compete
for the enzyme which degrades the prescription antihistamine terfenadine
(SeldaneTM). It may happen that the new metabolite of something is
a cell toxin and will wreck your liver; this is a proposed mechanism for
acetaminophen toxicity. If you are worried, there are blood tests which
can assess liver function.

Finally, I received anecdotal evidence from one person about potential
kidney damage. This person had used DXM numerous times without problem
until once (after a year of regular use) when, while using during a
flu, experienced kidney dysfunction and bloody urine. Years later when
trying DXM again, the effect repeated itself, with kidney pain, lack of
urine production, and (a few days later when her kidneys started to
produce urine again), blood in the urine.

Needless to say if this happens to you, it's a good sign you should stop.

Although some authors have suggested the possibility of DXM-induced
bromism (144), actual blood tests have revealed little danger
to occasional users, even with large doses of DXM (136). Daily use
might lead to a dangerous buildup. Notable symptoms of bromide
poisoning include headache, irritation, slurred speech, psychosis,
weight loss, hallucinations, and an acne-like rash. Bromism can cause
irreversible brain damage. In addition to directly testing bromide
ion content of the blood, bromism can be detected by increased anion gap.

DXM may decrease immune function due to sigma activity (51).
Chronic use of NMDA antagonists
seems to modify alcohol tolerance; this is based mostly on anecdotal
evidence and theory, but it appears to be a very real phenomenon.
If true, then it is important to note that the GABA receptor
effects of alcohol may NOT be changed; in practical terms, you
might be a lot drunker than you feel, and this could possibly
lead to alcohol poisoning. Be careful, and limit yourself to
as little alcohol as possible when using DXM. A recent paper
supports the ability of DXM to affect alcohol tolerance (53)
although this paper was concerned with a different effect, i.e.,
prevention of learned tolerance by NMDA antagonists.

At least one user has reported that very long-term regular use
of DXM (recreationally) can lead to a constant hacking dry cough.
I have not been able either to confirm or to disprove this.

There are obvious societal consequences to regularly using a drug which
can significantly alter or impair function, and though I shouldn't need
to bring this up, I'd better do so anyway. One user of DXM who sent me
email reported that he had lost his job, his wife, and his friends because
his regular use of DXM made him unable to function in society. He seemed
happy, and perhaps he found his own curious form of nirvana, but if he had
been given the choice before using DXM with foreknowledge of the
consequences he might have chosen differently.

I realize that most people go through irresponsible phases where they don't
really care about the consequences of their actions. Now, I truly believe
that, as long as those consequences don't involve the physical harm
to others, that's your business. Someone who cares about you has every
right to try to talk you out of it, but ultimately, it's your life, and
all too often people see any behaviour they don't understand (or like)
as self-destructive. I've known racists who believed that associating
with members of other races was self-destructive, and that certainly
doesn't make it true.

However, before doing anything that may change your outlook on life
significantly, ask yourself if you are ready for the changes that may occur,
for the loss of those things you now consider significant. Ideally one
would consider this before making any big decision in life, regardless of
whether it is marraige, divorce, taking a new job, becoming a Tibetan
monk, joining the French Foreign Legion, or doing too many drugs.

Remember though, that regular use of DXM may cause long-lasting, even
permanent changes in consciousness, mental ability, and personality.
Don't jump into the deep end without knowing how to swim and knowing
what's waiting for you down there.

One word: don't. Dissociatives seriously affect fetal brain
development (198), and reduce the number of axons pruned during brain development
(up to and including early childhood) (237). This results in disrupted
network formation (242), which leads to impaired spatial learning (246)
and may increase the chance of seizures. To sum this up in non-scientific
terms, kids whose parents used dissociatives during pregnancy run a high
chance of brain damage and possibly epilepsy.

When NMDA antagonists were first studied they seemed like a dream come
true: here were drugs which could block from part to all of the damage from
strokes, head injury, hypoxia, polio, and a variety of other conditions.
However, it seems that nature never gives something for nothing, and here
too there was another side to the coin.

The dream ended when Olney et al. demonstrated that animals given huge
doses of dizocilpine (MK-801), a new dissociative used in research, showed
curious vacuoles (essentially, tiny holes) in tissue samples in the posterior
cingulate cortex and retrosplenial cortex of lab animals
(174,177,180-182,217,307-308,323,329). Further research
showed that other indicators of damage were present, such as proliferation
of microglia and induction of a protein called HSP70
(Heat-Shock Protein 70) (173,325).

Since then, Onley's lesions, also known as NMDA Antagonist Neurotoxicity
or NAN, have been discovered with ketamine (325), PCP (302), and
dextrorphan (177), all noncompetitive NMDA antagonists. Competitive NMDA
antagonists have also been shown to cause Olney's lesions (213,312). PCP
causes additional damage to the cerebellum and other areas, possibly due
to its unique pharmacology (302). Drugs which bind to the polyamine site
on the NMDA receptor evidently do not cause Olney's lesions (318), although
nobody is quite sure why. Curiously, NAN may be worse in females than in
males (290).

The mechanism for Olney's damage is still being sorted out, and is somewhat
perplexing, since NMDA antagonists generally protect neural tissue from
damage rather than causing it. Trying to tie everything together is a little
like trying to solve a crime with only circumstantial evidence; there are
clues, but nobody's been able to watch the criminal in action. Here is what
current research seems to indicate, pieced together into a coherent whole.
A simplified explanation is given below.

Dissociative anaesthetics activate neurons in the posterior cingulate
cortex (PC) and retrosplenial cortex (RC) in lab animals (and
presumably humans) (289,310,322). There is also secondary, "downstream"
activation of neurons in the entorhinal cortex, dentate gyrus of the
hippocampus, and olfactory regions (213).
There are two theories for why this happens; either one, both, or neither
could be true. One theory is that NMDA receptors are found on inhibitory
GABA interneurons, and that when these receptors are bocked, these
interneurons secrete less GABA, and thus excitatory pyramidal neurons that
normally receive a lot of GABA inhibition are overexcited.
The other theory is that the PC and RC are less affected by NMDA
blockade than the hippocampus (and related areas), and that these
formations serve as feedback to the hippocampus and surrounding
networks. As these limbic networks are inhibited, the PC and RC
increase their output to compensate, resulting in overactivity (300).

Regardless of the mechanism, or whether the mechanism is none of
the above, the overactivity seems to cause intracellular
organelles (notably mitochondria and endoplasmic reticulum) to
malfunction (174,182,217).

The mitochondria probably lose their proton gradient and
allow their innards to spill into the surrounding cell material,
where they cause all sorts of trouble, possibly including forming
free radicals which cause further damage to the cell. Another
possibility is that the free radicals come first, and they
cause damage to the mitochondria and other organelles.
Mitochondrial damage can occur within 15 minutes of the drug dose,
the endoplasmic reticulum is damaged 30 minutes, and in both cases
gets worse as time progresses (308).

The cell responds to this damage with a protein called HSP70.
This "heat shock" protein is made and activated when something
(such as overheating, thus the name "heat shock protein" or HSP)
is causing a cell to malfunction so badly as to be in danger of
self-destructing, and its job is to turn the cell off until
repairs can be made (325). Hopefully, the cell will get
a lot of rest (about 24 hours (322)) until it goes back to
normal. At this point the problem is still reversible and
the brain cells have not been permanently damaged (177).

If the cell continues to be overexcited, it eventually burns
out completely as the increased temperature, disrupted ion
gradient, hypoxia, calcium ions, free radicals, and/or buildup
of waste products kill it. At this point, surrounding support
cells called microglia are activated and come in and eat the cell
(probably under the theory that if an infectious organism caused
the cell death, it'd better be destroyed before the infection can
spread) (173,325).

Then, scientists come along, freeze the brain, and slice it up
into thin slivers. During the fixing process (307), the
disrupted intracellular organelles expand to form vacuoles,
the HSP70 shows up with tests designed to look for it,
and the dead cells and proliferating microglia show up on
microscope slides.

The scientists take pictures, publish papers, thank their lucky
stars that they aren't the rats who just took ten times the human
anaesthetic dose of dizocilpine, and go home and fix martinis,
smoke cigarettes, eat fast food, and engage in other sanctioned
risk-taking behaviour (that's a joke ... yes I know there's a
difference between a behaviour that kills you in twenty years and
one which causes immediate brain damage).

A layman's explanation of the above: when you take too high a dose of
dissociatives, a few parts of your brain become wildly overexcited,
the brain cells get damaged, try to shut down, and (if damaged beyond
repair) die. Support cells come in to clean up the mess, and you're
left with permanent brain damage.

According to most current research the dosages at which Olney's lesions
become relevant is far in excess of human recreational doses. Here are
some of the reported dosages applicable for different dissociatives.

Obviously there are still a lot of questions to be answered. The most
important for human users of dissociatives is whether this type of damage
can occur at recreational levels, and if so, what can be done about it.

Let's review the evidence both for and against Olney's lesions in
human users of dissociatives. First, the evidence for. The posterior
cingulate and retrosplenial cortex (PC and RC) are involved in skills which
seem to be impaired in regular users of dissociatives. Olney's
lesions occur at doses several times the recreational dose, but that's
at one dose of the drug; repeated doses of lower amounts may cause the
same damage. Olney's lesions are also only generally visible
when large numbers of cells are destroyed, and they're significant
enough to be visible under the microscope. Finally, conditions
which increase the likelihood of Olney's lesions, such as less than ideal
blood circulation to the brain, large amounts of glucose (like that
found in cough syrup), concurrent use of stimulants, physical stress,
hypertension, and the like, are all commonly found in drug users, who
don't tend to be the healthiest lot (this is a generalization, of course).

On the other hand, Onley's lesions have never been found at human
recreational levels, and DXM has received little attention. Ketamine
users, some of whom have used ketamine for many years, don't typically
show mental impairment.
Even the few DXM users who do show impairment typically return to normal
after staying off DXM for several months, and at least one paper suggests
the mental impairment from dissociatives may be caused by depression, not
brain damage (355). DXM is typically found in hydrobromide form, and
bromide is a CNS depressant and may prevent damage to the PC/RC
(incidentally, that's not the reason DXM HBr is used; DXM HBr just happens
to be more water-soluble than any other form). DXM syrups usually
contain alcohol, which also depresses the CNS. And, the lower plateaus
of DXM are equivalent to doses of ketamine and PCP lower than commonly
used recreationally.

Weighing the two sides I personally believe that moderate use of
dissociatives is probably no harder on your brain cells than moderate
use of alcohol or amphetamines (I said moderate use, not some five
day fry-yer-brain speedfreak binge), and that if you use
DXM sparingly (e.g., once or
twice a month at lower plateaus, maybe once or twice a year at upper
plateaus), you'll be just fine. In fact, I've never known anyone to
suffer lasting impairment even after going through a few months of weekly
DXM use at upper plateaus. But I could be wrong! Mild brain
damage has a nasty way of showing up years later when you've forgotten
about the stupid things you did when you were young.

Nobody's totally sure exactly what most parts of the brain do, but there is
some evidence which may indicate possible functions for the posterior cingulate
and retrosplenial cortex. Although our understanding is far from complete,
and mine is considerably worse than that, I'll try to put together the
published results into a coherent whole.

The posterior cingulate cortex is the posterior (rear) part of the
cingulate cortex, a section of the cerebral cortex interconnected with the
limbic areas. The front part of the cingulate cortex is called,
appropriately enough, the anterior cingulate cortex. Like most areas of
the brain, the boundaries of the cingulate cortex are somewhat indistinct.
There are differences between the posterior and anterior cingulate cortex
(beyond the obvious one of location); notably, the anterior cingulate
cortex has fewer pyramidal neurons than the posterior cingulate, and in
the anterior cingulate these neurons have more complex connections (310).
This entire area may relay information between the hippocampus (and other
limbic systems) and other areas of the brain (298).

There is a lot of disconnected research that points towards possible
purposes for the posterior cingulate cortex. It may be one of the components
of verbal and auditory memory (294), multisensory perception (315),
visuospatial cognition and/or
evaluation of emotional behaviour (316). The right hemisphere
posterior cingulate is activated in comprehension of metaphors (303), and
the left in associative learning (304). Story comprehension seems to
use the posterior cingulate (292). In late Alzheimer's disease the
posterior cingulate may be subject to atrophy (314,317). It is activated during
anxiety (313) and in OCD (Obsessive-Compulsive Disorder) (305) but
deactivated during phobic fear (299).

It has been suggested that the cingulate cortex in general may be involved in
evaluating (posterior) and acting on (anterior) one's own behaviour and
spatial orientation (316). This is, in my opinion, the most comprehensive
view of the existing research. To put it simply, the job of the
posterior cingulate cortex might be to evaluate and consider where you are
and what you're doing. Since dissociatives tend to interfere with the
ability to evaluate one's own behaviour, it may be that the posterior
cingulate is a part of a self-evaluation system.

Another paper (311) analyzed the network properties of the
posterior cingulate, and suggested that neural output from the hippocampus
that was in sync with the theta rhythm would pass through the posterior
cingulate cortex in preference to other routes. What makes this so
interesting is that the flanging or strobing effects of DXM seem to occur
at theta rhythm, which may be a consequence of DXM's effects on the
posterior cingulate.

There was considerably less information published on the retrosplenial
cortex. One paper found that it was activated during the encoding of
novel situations (321). Another (324) suggests that the circuitry between
the retrosplenial cortex and hippocampus is an important path by which the
hippocampus affects learning, memory, and emotional behaviour. Numerous
papers suggest it has a role in visual processing.

Hopefully I'll be able to fill this area in with more information as my
knowledge of (and the amount of published information on) these two
areas of the brain increase. Until then, make what you will of the rather
sparse information I have provided.

So what can you do about this? Well the best thing I can tell you is, stay
away from drugs that might give you brain damage, whether it's DXM, alcohol,
stimulants, benzodiazepines, PCP, or glue. If marijuana were legal I'd say
smoke as much as you want (keep in mind that the smoke isn't terribly
good for your lungs though), since there have been numerous studies which have
shown no neurotoxic effect from marijuana. But since marijuana ain't legal,
... well, there's always caffeine I guess (until that's made illegal too).

Realistically, I know many of you are going to keep using DXM, especially
since it obviously doesn't impair everyone who uses it (even in large
amounts). People regularly make choices to engage in risk-taking
behaviour, whether it's rock climbing, driving too fast (or without a
seat belt), eating red meat, not exercising, or taking drugs. Ultimately
that's your choice. Society has made many drugs illegal, and many argue
that if drugs were legalized that would give them an aura of legitimacy
and safety, but it's legal to sit around and watch TV all day, eat nothing
but cheeseburgers, bathe only once a month, and hit yourself on the head with
a hammer, and even as a child I never believed that legality made any of these
a good idea.

So here are some practical suggestions based on research into Olney's
lesions, which may work, may do nothing at all, or may make it worse. It's
up to you to decide, but keep in mind that tomorrow it may turn out that
any one of these is helping to fry your brain.

Avoid stimulants of any kind with DXM, especially yohimbine.
Alpha2 agonists seem to prevent Olney's lesions
(175); yohimbine, an alpha2 antagonist, could
instead make the problem much, much worse.

Make sure you are in good physical condition, with low
blood pressure and low cholesterol. The ability of brain
cells to recover from metabolic insults is vastly improved
if cerebral blood circulation is in good shape.

Consider Coenzyme Q10 supplementation. One paper suggested
that Q10 might be useful in some types of neural lesions
(216). It has been suggested that,
as a mitochondrial energy substrate, it may prevent brain
cells from "running out of fuel".

Consider a very mild CNS depressant, like a glass of
wine or a beer. I wouldn't go much beyond this, since
combining DXM with too much alcohol can lead to severe
nausea. A benzodiazepine is probably overkill.

Use gelcaps or capsules instead of syrups, which contain
glucose; the presence of high glucose levels seems to make
things worse.

Limit use of DXM extract, which doesn't contain bromide ions,
or use it in conjunction with a little alcohol.

Limit frequency and dosage of DXM

Give your brain a rest of at least 48 hours after using DXM

Eat healthily before, during, and after DXM use

Consider an alpha2 agonist (175). Or maybe not; the research
isn't conclusive on this yet.

Regularly monitor your mental skills and have others monitor
them as well.

Make each DXM trip count so you don't feel the urge to reattempt
an unfulfilling trip experience.

From one viewpoint, of course, anything can be addictive -- television,
chocolate, masturbation, self-mutilation, etc. So in that sense,
yes, DXM can be addictive. Somewhat more relevant are the degree
to which DXM is addictive, and how such addiction manifests itself.
The quick answer is, DXM can be addictive if you use too much, too
often.

The traditional distinction made with respect to addiction is
between physical addiction and psychological addiction. As examples,
alcohol is physically addictive, whereas marijuana is psychologically
addictive. Unfortunately this distinction has its problems -
not the least of which is that since the brain is a physical construct,
any addiction is in some sense "physical."

As physical addiction is a somewhat nebulous concept at best,
I prefer to use the concrete ideas of tolerance and serious withdrawal
symptoms. Tolerance is a process by which the body and brain
adjust to a drug so that the dosage must be increased to achieve
the same effect (some drugs, such as nitrous oxide, exhibit reverse
tolerance, becoming more potent the more often they are used).
"Serious" withdrawal symptoms is somewhat
less clear, unfortunately. Note that it is possible to become
tolerant to a drug without being psychologically addicted; in
fact, some people lose the desire to use a drug when tolerance
takes away its more interesting effects.

There is considerable evidence based on personal reports that tolerance
to DXM's more interesting dissociative effects builds quickly.
This is a result of upregulation or sensitization of NMDA receptors,
as well as possible changes in other receptors and systems indirectly
affected by DXM. Cross-tolerance exists between DXM, PCP and
ketamine, naturally. Some people seem to be immune to tolerance
to dissociatives including DXM (lucky them).

Usually it takes several doses before tolerance is noticeable,
although a few people have noted tolerance after just one dose.
Larger doses will lead to quicker tolerance. Once tolerance
has built, it takes at least three weeks before receptors will
reregulate to normal levels. To avoid this problem, it is probably
best to dose only once a week at most. Also, some people believe
that receptors which are upregulated (or downregulated) for long
periods of time may tend to stay that way. The practical upshot
is you should take a month off every now and then (a good idea
with any drug, incidentally).

Interestingly, the first plateau music euphoria
effect also seems to disappear with repeated use of DXM. It's
also one of the last effects to come back. This may be due to
downregulation of dopamine receptors rather than upregulation
of NMDA receptors. The practical upshot is, don't do DXM all
the time. Again, some people are luckily immune to this tolerance
effect.

For information on withdrawal and withdrawal symptoms, refer to the
next section.

Psychological addiction to DXM has been noted a few times, and
can theoretically lead to physical addiction. Generally, though,
dissociatives aren't considered particularly habit-forming, since
they tend to have such "heavy" effects. Low-dose DXM
might be an exception due to its moderate to strong stimulant
effect; in practicality, it's probably too hard to consistently
hit the first plateau.

There are exceptions, some of them notable. One case report (132)
involved a 23-year old male who maintained an incredible daily
dose of 30 mg/kg to 40 mg/kg DXM (plus a six-pack of beer)! Needless
to say, after maintaining this dose long enough, he had become
addicted, although the authors consider it a "psychological"
addiction, with withdrawal symptoms such as dysphoria, depression,
and anxiety.

Most people who use DXM have noticed little or no addiction, and
only mild tolerance (don't let that scare you; remember that coffee
produces both tolerance and withdrawal symptoms). A few unfortunate
people have developed problems with DXM. Prolonged, heavy use
of DXM seems to induce dysphoria, anxiety, and/or depression in
some people; as the dosage is increased, the problem gets worse.
Unfortunately, at this point, there may be withdrawal problems
(see the next section). If this happens to you, seek medical
assistance.

Withdrawal from occasional DXM use is almost certainly
not dangerous, and in fact any "symptoms" felt are probably
just "jonesing" - the same sort of withdrawal "symptoms"
felt with marijuana, television, sex, etc. At this point it's
a matter of willpower more than anything else.

Once tolerance has built, withdrawal has the potential to cause
more serious problems. Mild tolerance to DXM is probably no more
dangerous than mild tolerance to alcohol (tolerance at the level
of "being able to hold your liquor"). Withdrawal may
produce boredom and mild anxiety, but rarely anything more troubling
than that.

One person reported a curious withdrawal effect which has also been
noted upon cessation of SSRI antidepressant therapy. Whenever moving
his eyes, or upon any sudden change in sensory input, he experienced
a sudden, momentary dizziness and altered consciousness. Ginkgo biloba,
exercise, and sleep were reported to all help with this.

Beyond the mild tolerance level, things could get rapidly worse. There
is evidence that significant NMDA upregulation can lead to (100)
and many of the symptoms of opiate withdrawal may occur via a similar
mechanism (109,133). The good news is, studies
generally haven't found any significant evidence of brain damage
from heroin withdrawal, so withdrawal from DXM probably wouldn't
be much trouble. The bad news is, heroin withdrawal isn't particularly
enjoyable.

Interestingly, one person who developed addiction and tolerance
to DXM also compared the withdrawal symptoms to those of heroin
(although DXM never produced any of the positive effects of opiates
in this individual). These symptoms included watery eyes, stuffy
nose, gooseflesh, muscle spasms, increased pain sensitivity, nausea,
anxiety, and depression. Furthermore, the individual eventually
began to develop some of these symptoms even while using DXM.
This is definitely something to avoid.

If you happen to develop a significant degree of tolerance to
DXM, it might be a good idea not to quit "cold turkey"
(all at once). Build down slowly over a few weeks, and avoid
all other drugs in the mean time. One person who had been using
DXM twice daily reported no withdrawal symptoms after decreasing
the dosage 10% per day, and stopping at 180 mg. This should prevent
any excitotoxic rebound.

On the other hand, given the research from Olney et al (see
Section 6.3.1, it may be better to go ahead and quit cold
turkey after all. Some research casts doubt upon upregulation
of NMDA receptors with blockade, and if so, then there
may be no danger to quitting DXM completely without tapering
down. To be honest, there is evidence on both sides, and the best
advice I can give you is not to get into this situation in the
first place. If you do manage to develop a DXM addiction, I wish
you the best of luck, and I think your best course of action would
be to see a physician. Since most medical authorities are ignorant
of DXM's psychoactive potential, it would probably be advisable to
treat it as an addiction to any other dissociative (ketamine or
PCP).

The first thing to understand about DXM addiction is that most people who
find themselves addicted use DXM on a very regular basis -- weekly, or
(more frequently) daily. This is very dangerous!. It is vital
that you quit using DXM as quickly as possible if you are using it on
a daily basis.

If you have access to mental health services I strongly suggest you seek
them out. Many areas provide financial assistance for uninsured or
low-income patients. DXM addiction can be treated like addiction to any
other dissociative, i.e., PCP or ketamine. Unfortunately, many physicians
and psychiatrists are not generally up-to-date on dissociative addiction,
so you may need to look around.

The biggest problem with DXM addiction is rebound depression. Many casual
DXM users have noticed a slight depression during the hangover phase. With
regular use, however, the brain becomes tolerant to certain aspects of the
DXM experience (probably a reregulation of serotonin receptors due to the
DXM-induced serotonin release). To compensate for the depression (which
can be severe) many people turn back to DXM. Unfortunately, dissociatives
make poor antidepressants, since they have numerous side effects.

Incidentally, keep in mind that dissociative-induced depression is often
severe enough to result in impaired mental functioning. Many cases of
dissociative "brain damage" turn out not to be permanent after all, but
only the consequences of major depression.

If you choose to kick the habit on your own, or if you have no other choice,
you have two options: build-down and cold turkey. Build-down
means that you slowly taper off DXM use in the hope that your brain will
readjust as you do so, and thus avoid the potentially severe depression of
sudden withdrawal. Cold turkey withdrawal (the term comes from the
gooseflesh of heroin withdrawal) means stopping suddenly.

The first and most important step in either case is wanting to quit. Not
merely knowing you should, but actually wanting to. Take a good, hard
look at your life. Talk to your friends about your problem -- I know it
can be hard to do, but they probably already know it anyway. Examine
your performance at work or school. And look at your own use patterns --
are you using DXM as a group activity, or are you using it alone? Take
stock of your finances. All of these factors can help to contribute towards
the desire to quit DXM.

Keep in mind that you may have to quit DXM permanently, and never
use it again. By the time most people has become addicted to DXM, however,
they tend to derive little or no pleasure from the experience anyway. So
you must be prepared for the thought of never using DXM again, or at least
waiting a year or two and before trying it again. Remember, though, there
are other psychedelics out there, and many of the more interesting effects
of DXM can be achieved through transcendental meditation, yoga, and other
spiritual work.

In preparation for quitting any drug, get rid of anything and everything
that acts as a "trigger" for DXM use. Let your friends who use DXM know
you are trying to quit. You don't have to shun them completely, but you
might be well-advised to avoid them while they are using or discussing
DXM. Discard any supplies of DXM you have (if you are quitting cold-
turkey). Don't go to the drugstore without someone else to watch over
you. Don't go to places where you traditionally used DXM (this is hard
if you used it at home). If you will be moving soon, you can use the
move as an opportunity to leave behind all the sensory triggers that
made you think about DXM.

The safest way to quit from a neurological standpoint is to quit cold
turkey -- completely and suddenly. This is also the most difficult.
The depression stage can last for several weeks, even months. Fortunately,
it is treatable with drugs; SSRIs such as fluoxetine (Prozac) have been
used with great success in treating PCP addiction, although there is some
evidence that serotonin/dopamine reuptake inhibitors, or combining a
SSRI with a dopamine reuptake inhibitor such as bupropion (Wellbutrin),
may be preferrable. In drug-resistant cases, electroconvulsive therapy (ECT),
or the newer (and safer) variant, left-prefrontal transcranial magnetic
stimulation, have been used as well. In any event, it is important to
see a psychiatrist who can assist you, give you a neurological evaluation,
and prescribe any necessary drugs. DO NOT use DXM after you are
placed on antidepressants of any kind.

If you do not have access to psychiatric medicine, you still have other
options. Try to vary your daily routine to expose yourself to new and
interesting stimuli. As corny as it seems, taking long walks in the
woods and, especially, getting a lot of sunlight, has helped many people
(and there may be some evidence that DXM-induced depression may be in
part due to a disruption of the circadian rhythm, similar to Seasonal
Affective Disorder). Keep a regular, rigid schedule of getting up and
going to bed at the same time. Some people have had success using
melatonin to help them stay on schedule but there is some evidence that
melatonin may worsen depression in susceptible individuals. And the
most important thing you can do is to get regular physical exercise!
Not only does it help with depression, it also helps to get your body
and brain back in top working order.

Build-down is a controversial method for dealing with addiction. Many
people with whom I've spoken have used build-down successfully, but
many others tried it and failed. At the very least you can try it first
and then, if that doesn't work, try cold-turkey withdrawal (which may
be easier after you have cut down DXM use).

There are two conflicting issues here. On the one hand, maintaining
a regular, even dose of any drug can prevent the "rush" that so many
people find contributes to the addictiveness of the drug. On the other
hand, regular use of DXM can become dangerous to the brain. Weighing
these issues, and on the basis of those who have used build-down
successfully, I believe that a regular low dose of DXM may be
appropriate for build-down. Fortunately, even a lower dose of DXM
seems to help fight off dissociative depression.

I do not claim to be a physician and I can only relay to you what others
have told me. Before attempting build-down you must consult a
medical authority, and at the very least have your serum bromide level
checked (or check anion gap, which amounts to the same thing) to see if
you are already in danger or bromide poisoning. Assuming you check out
OK, and your physician is willing to let you try build-down, here is
what I have been told from successful build-down attempts. THIS
IS NOT INTENDED AS MEDICAL ADVICE, ONLY ANECDOTAL EVIDENCE FROM FORMER
DXM USERS.

First off, get someone else to help you -- a friend, spouse, whatever.
You want to make sure they will keep you on the rigorous schedule and
not let you go back to using large amounts of DXM.

The key to this method, according to those who have used it successfully,
is to place yourself on a regular, low dose of DXM -- just enough to
keep the depression from becoming severe. First off, wait at least three
days from your last DXM dose before starting the build-down; this should
allow your body to clear out any DXM and metabolites. Also, make sure you
are not on any drug which can alter DXM metabolism -- including
antidepressants.

The build-down dose is taken three times per day at rigid six hour
intervals, and an individual dose should not be enough to get you
high. One person successfully used 30 mg 3/day; most however have used
60 mg 3/day. It would probably be better to start at 30 mg 3/day and then
move up, if that isn't working, after two or thee days.

After establishing the maintenance dose, build-down users continued this
dose for one to two weeks, before halving the dose. Again, after another
one to two weeks, the dose was halved again; finally, when the total daily
dose was less than 45 mg, they went to twice a day for one week, then
once a day for one week, and then quit completely.

All of the people who built down experienced mild depression, although
most found it manageable, and some told me that the ideas suggested above
in Section 6.8.2 (exercise, walks in the woods, sunlight,
regular sleep habits, etc.) helped to make them feel better.

Again, remember, I'm only conveying anecdotal information here; you
absolutely must work with a physician or counselor who can give
you the professional help you need. For all I know, these people who
told me their successes could be unique in some way (or for that matter
they could be lying to me).

Possibly never. Like any other severe addiction, there is always the
risk of a relapse. If you choose to throw caution to the wind, that's
your choice and you do it with the understanding of the risks involved.
The only suggestion I can give you is to limit DXM use to one particular
environment, and make sure it's an environment you do not encounter when
not using DXM. Basically, by making it into an isolated ritual, you
lessen the chances of normal sensory cues leading you back into addiction.
One former DXM addict managed to use DXM again without becoming addicted
after two years of being drug-free; he did so by only using it with a
select group of people, in one particular place, and then one of his
friends was responsible for giving him his dose in a particular cup (thus
avoiding the sensory cue of the cough syrup bottle).

Still, it's better to find other ways of feeling good. Yoga and meditation
are probably the two best means of achieving altered states of consciousness
that are similar to DXM (unfortunately, unlike DXM, they require hard work
and patience). If you live somewhere where serotonergic psychedelics
(mushrooms, LSD, 2CB, etc) are legal, you may find that these can give you
the psychedelic consciousness without the addictiveness (or danger of
neurological damage) that come with DXM.

Best of luck, and remember, above all, seek professional help. I am not
a physician, only a researcher, and I cannot and will not claim to give
advice for your particular case. There are too many other factors which
I do not know, and cannot understand, as I have limited medical knowledge
in areas other than neuroscience.

Hangovers from DXM trips are not common at lower dosage ranges
(first and second plateau). Instead, many people report feeling
energetic and refreshed the next day, although it seems that getting
enough sleep is important here.

At higher dosage levels (third and fourth plateau), hangovers
are more frequent. Hangover effects reported consist of lethargy,
sleepiness, amotivation, mild sensory dissociation, muscle rigidity,
muscle tics (especially in the jaw and hands), dizziness, loss
of balance, headache, photophobia, and sharply diminished sense
of taste. Some people say that everything tastes like slightly
salty tepid water, or like MSG (monosodium glutamate, the flavor
enhancer). Note that you're very unlikely to get all, or even
most, of these symptoms.

Some of the hangover effect from high dosage trips is probably
due to residual DXM or dextrorphan, especially in individuals
who lack P450-2D6, or in whom it is inhibited (e.g., by fluoxetine).
To my knowledge there doesn't seem to be any way to speed up
the metabolism; the best I can suggest is to exercise, drink plenty
of water, take a multivitamin every day (don't overdo it, one
is plenty) and possibly a small iron supplement (which
just might increase cytochrome turnover), get enough sleep, and
eat right. Don't take too much iron; iron is very toxic.

Other hangover effects may be due to neurotransmitter depletion
(due to induction of 5HT and dopamine release), temporary inactivation
of NMDA receptors (I doubt it, but there's been speculation),
or just plain lack of sleep. Again, treating your body well is
probably the best you can do.

Finally, there is evidence that, for 24 to 48 hours following use of a
dissociative, certain parts of the brain are underactive (probably due
to neurotransmitter depletion) (322). There's not much you can do
except tough it out. Obviously, you shouldn't use DXM unless you have
a day to recover.

Preventing hangovers may be possible to some degree. Certainly,
make sure you are in good physical condition to start with, and
don't try to stay up too late during your trip. Drink plenty
of fluids (it is possible to get dehydrated; this can slow down
the kidneys), and don't mix DXM with anything that could
further deplete neurotransmitters (e.g., amphetamines, MDMA, etc.).
Try to avoid going to sleep while still tripping hard - it seems
to reduce the quality of sleep. Eat something before you go to
sleep; usually DXM kills the appetite, so you may not know your
body needs food.

Another possibility is the use of nootropics ("Smart Drugs") to help
prevent and alleviate hangovers. A good place to start for
information is alt.psychoactives (although, like any source on the
Internet, take any information with a grain of salt and ask for
medical journal references); another good place is Dean and
Morganthaler's text on the subject. A healthy dose of skepticism
is probably a good idea here; some of it might be placebo effect.
There's evidence for and against; check Medline if you're interested.
Note that unless otherwise specified, everything I mention should be
available at health-food or mail-order vitamin suppliers (this is USA;
I don't know about other countries).

Several people have reported beneficial effects from cholinergics,
specifically choline (the precursor to acetylcholine), and DMAE
(also a precursor, and a choline oxidase inhibitor). In both
cases the bitartrate salt seems to be the usual (there is a liquid
DMAE para-aminobenzoic acid formulation that tastes nasty and
evidently doesn't work). Note that some people with depression,
primarily endogenous, react very poorly to cholinergics. Also
note that they can make you really, really irritable if you're
susceptible. Regular use of DMAE seems to be the most effective,
although that's something that you have to build up for a couple
of weeks (Dean and Morganthaler suggest around 800 mg per day in
divided doses).

One-time use of DMAE or choline immediately before, during, or
after the trip has also been reported to work, (in that order
of preference), although not as well. Recommendations given to
me have been 800 mg DMAE, or 1500 mg choline; in either case with
350 mg vitamin B-5 (pantothenic acid) which acts as the relevant
cofactor here. Don't go much above that.

There is some preliminary evidence that supplementary tyrosine (the precursor
to dopamine and noradrenaline) may actually be useful in the case
of dopamine depletion. Normally, the rate-limiting enzyme in
the process is nearly saturated, so boosting tyrosine doesn't
work. It's hypothesized that more enzyme may be produced in response
to dopamine depletion. Furthermore, sigma activity may enhance
synthesis of dopamine (114), so taking supplemental
tyrosine is even more likely to be a good idea.

A side note ... for whatever reason, nootropics fans seem to be abnormally
fond of using phenylalanine instead of tyrosine. Phenylalanine does convert
to tyrosine, but it's a very slow, limited conversion, and there's no good
reason for choosing phenylalanine over tyrosine.

Vasopressin might also be useful; it seems to have a fair amount
of success in combating intoxicants, possibly by affecting long-term
potentiation (how I don't know). It's prescription in the USA,
and it does have side effects.

One final note - do not take tryptophan! Although this
isn't established, it's possible that NMDA receptors may be upregulated
after a DXM trip (especially in chronic users). Tryptophan, in
addition to leading to 5HT, also leads (along a much more efficient
pathway) to a substance called quinolinic acid,
which is very toxic to neurons, and acts via NMDA receptors.

The LD50 (dose at which 50% of animals die) of DXM
doesn't seem to be well known. For a variety of reasons, animal
assays of the lethal dose of psychoactives aren't always accurate.
Nor have I ever found a published LD50 for DXM. So
instead, I've decided to go on the basis of the few deaths that
have occurred from DXM use, keeping in mind the amount of DXM
people regularly consume for recreational purposes.

In searching medical literature, I found only two cases of death
associated with DXM use, both in Sweden. In one case, a girl
was found dead in a public bathroom with two bottles of 30 mg DXM
tablets (the number of tablets is believed to be 50/bottle, but
may be 15 or 25). She had previously tried to commit suicide
using a bottle of 50 tablets (this leads me to believe that she
had, in fact, taken 100 tablets, for a total dose of 3000 mg).

The other case involved a 27 year old man, and few details were
specified. In both cases, death was apparently due to inhibition
of respiration. Plasma levels of DXM were 9.2 and 3.3 micrograms
per gram (cases 1 and 2); plasma levels of dextrorphan were 2.9
and 1.5 micrograms per gram. Liver levels of DXM were about an
order of magnitude higher. In both cases, the ratio of DXM to
dextrorphan was about 3 (9).

On the other hand, a dosage of 42 mg/kg/day has been used (with
respiratory support) in
children (33), which would be 2500 to 3000 mg for a 60-70 kg adult. There
is also a very low incidence of death associated with DXM use.
Since a 42 mg/kg dose in an adult may be stronger than the equivalent
dose in a child (I have no reason to believe this, but it is possible),
caution is advisable in taking this as an indication of safety.

The highest daily dose of DXM I've come across is from a case
study of a 23-year old male (132). His daily dose was 3 to 4
12oz bottles of Robitussin DMTM, for a total of 2160 mg (31 mg/kg)
to 2880 mg (41 mg/kg). He was, of course, considerably addicted
to DXM, and had built up this dose over a long period of time.

It is reasonable to expect, given the data, and the available
data on the effects of high DXM doses, that DXM starts becoming
toxic around 25 to 30 mg/kg (about 1700-2000 mg for adult of 150 lb).
This corresponds to between 5 and 6 4oz bottles of 3 mg/ml cough
syrup, i.e., a fairly large amount, but still within the realm
of hardcore experimenters. Keep this in mind before you consider
large doses. IV naloxone is considered the antidote
for DXM overdose (54), even though DXM isn't an opiate.

Note that since publishing the FAQ, I have heard anecdotally (but have
not verified) of a few recent (non-fatal) overdoses in Australia, and one
fatality in the United States. The latter involved long-term regular
use and may have involved a buildup of DXM in the bloodstream. Nine
additional fatalities involving combined use of DXM and zipeprol in
Korea have been documented (367).

No. Definitely not. Use of medicine, OTC or not, contrary to
instructions may be a violation of local, state, and/or federal
law. I hereby specifically tell you not to use any DXM-containing
product (or any other product) in a manner inconsistent with its
labeling.

Even if DXM were legal for recreational use, I still wouldn't
recommend it for frequent use, nor for high-dosage use. Frequent
use may bring about undesirable changes as mentioned above. High-dosage
use carries with it all the risks of any hallucinogen, and can
be distinctly unpleasant. Very little is known about sigma, PCP,
or NMDA receptors. You dork with them at your own risk, and that
risk may be considerable.

To be honest, part of my answer is covering my ass, and part is genuine
caution. DXM probably isn't quite as friendly as I used to think it was,
and there's no need to place onesself in harm's way for the sake of a
buzz. If you're just looking to get generically "high", there are better
highs out there (unless you really happen to be drawn to dissociatives, and
if so, believe me, you have my sympathies). So make sure you really want
to do DXM before you do it. It's not a substitute for LSD or marijauana
and shouldn't be used as one.

Once more, I officially instruct you not to do DXM, or any other drug,
unless under the guidance of a physician. Right now, in the USA,
there are many people with nothing better to do than support legal
paternalism and legal moralism. For whatever reason, some people
feel that they have the right to tell a legal adult what she or
he can and cannot do that involves only her/his body. And as
long as this goes on, I'm going to make sure I'm not thrown into
prison so they can free murderers and rapists to make room for
me. So, I'm telling you - don't break the law.

This section covers suggestions for undesirable, unexpected, and
unplanned situations. Always remember, though, if you feel there
is a real emergency, get to a hospital. While DXM-related deaths
are very, very rare (two published, three anecdotal), they have occurred.
Nobody wants to see any more happen. None of this is intended to be
medical advice or replace the judgment of a physician, nor should it be taken
as such. These are general guidelines only, compiled from reports
of DXM users. Neither I nor anyone else take responsibility for
any injury, death, or other misfortune, resulting from this advice.
There, have I covered my ass well enough? Probably not. Just
remember, please use common sense and be careful!

Some people get the itch,
some don't. Among those who do, some seem to get it from the DXM
itself, some from the dyes in cough syrups (in particular tartrazine),
and some just as a consequence of losing tactile sensation.

In any case, from all reports the best thing seems to be to wait
for it to go away, and try to think about something else. Scratching
is OK, so long as you don't injure yourself in the process (remember,
you many not be feeling pain as you normally would). A loofah
can be quite enjoyable, actually, should you feel the urge to
take a bath (which evidently can itself be enjoyable on DXM.
Just be careful!) You can try a topical antihistamine spray,
but I doubt it will do any good. An oral antihistamine (remember,
never take non-drowsy antihistamines like SeldaneTM with DXM!) is
also reported to work without adverse effects.

If the itch is accompanied by a rash, swelling, or other symptoms
of an allergic reaction, you can consider taking a small dose of an oral antihistamine such as Chlorpheniramine Maleate (CPM)
(not a prescription one), and make sure there is someone with
you. Redness with itching often results from unconscious scratching or
rubbing the skin, but some DXM users report redness appears with the onset of
the itching reaction.

If the allergic reaction continues, or you feel you may
be going into shock, get to a hospital. To my knowledge this
type of allergic reaction has never occurred on DXM.

Many times this is more a problem of perception
than anything else. Still, it does happen. As far as I have
been able to determine, DXM itself can raise the heart rate somewhat,
about as much as a mild to moderate stimulant (e.g. a few cups
of coffee to a "coffee virgin"). Reports have indicated
a range of 90 to 120 beats per minute as the relevant range.

Try to have someone sober take your pulse, since you may be getting
sensory echoes. If your heart rate is truly high (as a general but
probably inadequate guideline, above 120 beats per minute), do your
best to relax, stay calm, and see if it goes down with relaxation
(and see Section 6.12.3 below if relevant). If you continue
to have an abnormally fast heartbeat, by all means see a doctor. You
probably aren't in much danger, but there's no need to take the risk.

Prolonged very fast heartbeat, or fast heartbeat accompanied by
chest pain or tightness, should be taken seriously and may be
cause for medical attention (note that a panic attack can also
cause a feeling of chest tightness). If in doubt, go to the hospital.
People with existing heart problems should avoid recreational DXM use.
Incidentally, neither of the recorded deaths due to DXM overdose were
attributed to heart failure (respiratory failure was considered the
cause).

Panic attacks can occur on DXM, especially in naive users
or users rushing in to higher doses. A panic attack can increase
the heart rate significantly, sometimes as high as 200 beats per
minute! Unfortunately, panic attacks can be hard to control;
the best thing to do seems to be to try to relax, go somewhere
you feel comfortable, and focus on your environment. A panic
attack is a positive feedback situation; once you start having
one, the symptoms themselves can feed the fear. Breaking this
vicious cycle can be difficult. If you are predisposed to panic
attacks you should probably avoid DXM in the first place.

An irregular heartbeat, like a fast
heartbeat, may be a problem of perception more than anything else.
Remember that, especially at higher doses, there can be a "sensory
echo" effect which may influence your measurements.

An occasional feeling that your heart "skipped a beat"
is usually not cause for worry. Sometimes it is due to spasms
of the esophagus, stomach, or bronchial tubes and has nothing
to do with the heart; it's hard to distinguish sensations among
internal organs. More frequent heart irregularity, or irregularity
with chest pain, may require medical attention. Go to the hospital
if in doubt.

Ah, the joys of ingesting large amounts of thickening agents.
Nausea is to be expected, especially with cough syrups.
It usually goes away. A few people have reported that meclizine (available
in several brands of over-the-counter anti-nausea medicine) can help
without adversely affecting the DXM experience. In general, though, most
anti-nausea drugs are anticholinergics and/or CNS depressants, neither
one of which you want to mix with DXM. The best response seems
to be to tough it out, or switch to gel-caps. Incidentally, avoid
taking DXM with greasy or heavy foods.

Vomiting occasionally occurs, usually for the same reason as nausea.
Again, not much to worry about. If you do vomit, just make sure
to drink lots of water to replace what you just lost. Both guaifenesin
and large amounts of alcohol tend to contribute to the tendency
to vomit.

Gas and diarrhea, especially after the trip, are also fairly common
with syrups. Not much to do, unfortunately; just tough it out
and drink water. Loperamide (ImmodiumTM) can help with intestinal
cramps and diarrhea, and from all reports doesn't affect the brain at
all.

This is mostly advice for the designated sober person; obviously
it won't do you much good if you're unconscious. Unconsciousness
with DXM is to my knowledge extremely rare (I've heard of it happening
once). Please keep in mind that it is possible to achieve a fully
anaesthetic dose of DXM, but if you do so you risk serious injury, and
probably won't remember much of the experience. There are probably a
few psychonauts out there with the experience (and the assistance of
physicians) to handle voluntary anaesthesia, but let's leave that to
the professionals and the truly insane.

Generally if someone passes out, the first thing to do is make
sure they don't fall and hit their head. Yes, DXM may protect
brain cells somewhat from the effects of head trauma, but let's
not try out that theory ourselves. Make sure the unconscious
person is lying down with their feet elevated, and that someone
(sober) is with them. If you feel there is any danger of vomiting,
roll the person onto his or her side.

There are several reasons why a person on DXM might be, or appear,
unconscious. Most commonly, he or she may be in an imaginary dream
world, unresponsive to the physical world. He or she may have fainted
due to postural hypotension (which I've heard of happening with DXM).
Or they may just be ignoring you.

Whatever the reason, try and get a response from the unconscious person.
If you can't get any response after a minute or so, it's time to call an
ambulance. See Section 6.12.7.

The first thing to do in the case of a suspected overdose is to call
an ambulance. Don't argue, don't hesitate, and don't worry about the
legal implications; you can work that out later. Remain calm; freaking
out won't help anyone. If they are unfamiliar with DXM overdoses,
tell them to bring a syringe of naloxone. If you receive instructions
from the medical authorities, follow them.

Check the individual's breathing and pulse. You may need to apply CPR
if the heart has stopped (again, follow any instructions the emergency
personnel give you). Try to find out exactly how much DXM he or she
took, and at what time. Also find out if he or she was taking any other
drugs (legal or not), notably including antidepressants, prescription
antihistamines, sedatives, or alcohol.

Really, at this point, you need competent medical advice, and I'm not
a physician. Unfortunately, as more than one physician has told me, the
medical community is generally ignorant about DXM. Given this, I'm going
to try to outline below as much as I can that might be relevant about DXM
in an emergency, with the understanding that someone with
medical knowledge will evaluate the situation.

When dealing with a DXM overdose it is important to remember that there
are really two drugs at work: DXM and its metabolite, dextorphan. At
overdose levels, the conversion enzyme (CYP-2D6) will probably be saturated,
so even after gastric lavage and activated charcoal, DXM will continue to be
converted to dextrorphan (DXO), probably raising serum DXO levels. Also,
since DXM is usually found as the hydrobromide, you may have to worry about
acute bromide toxicity.

DXO is in the same class as ketamine and PCP, and from all accounts can be
treated as such. DXM has additional pharmacological activity; it is a
calcium (and possibly sodium) channel blocker and a mild noncompetative
dopamine reuptake inhibitor. Like PCP, DXM may cause hypertension and
CVAs (though if it's any consolation the NMDA blockade should minimize the
damage). There is also the possibility for serotonin syndrome if DXM has
been combined with a serotonergic. Rhabdomyolysis has never been observed
with DXM but is possible.

I have no data on whether acidifying the urine will hasten DXM clearance.
Nor do I know whether DXM (or DXO) may reappear in bile, though I have
heard several anecdotal reports of increased bile secretion during DXM
use.

Finally, remember that, like PCP, DXM can cause emergence phenomena.
Once the individual regains consciousness he or she will probably be
confused, and possibly paranoid and hostile. Also like PCP, DXM can
impair perception of pain. Although I've never heard of it happening,
it's possible that someone coming out of a DXM overdose could become
violent.

Remember, if there is any indication or suspicion of an
overdose, get medical assistance immediately!

First, make sure you actually have a fever. DXM can mess with
your sense of temperature. On the other hand, I have received
one report of DXM-induced hyperthermia that could have been dangerous.
A temperature at or above 102 F (39 C) is entering the danger
zone. If this happens to you (or someone you are with), the best
way to cool down is by taking a cool bath or shower (make sure
it feels cool to a normal person!), and drinking cold water.
Incidentally, speaking from personal experience (with the flu,
not DXM), the "cool" water will feel damn cold.

In the case of a fever at or above 105 F (40.5 C) you've got a
real emergency on your hands. Immediately contact a doctor or
hospital, and try to reduce the body temperature as quickly as
possible. Ice-water baths are acceptable providing there is someone
(sober) there to make sure the person doesn't go into shock and drown.
Expect to hear a lot of screaming; this is a significantly unpleasant
experience even without a fever.

Again this is usually a perception problem, and sometimes is
related to panic attacks. There is also evidence that dissociative
anesthetics in general cause a transient feeling of shortness of
breath, possibly because the body is beginning to "take over"
breathing from conscious control. Take deep, even, and slow breaths;
hyperventilating won't help, and can make you feel even worse.
It should clear up by itself. In the case of hyperventilation,
the "breathing into a paper bag" trick really does work,
by increasing blood CO2 levels.

If you start feeling like you are choking on your tongue, make
sure someone can assist you, or call a doctor if you believe you
really are choking. There is actually very little danger of choking
on your tongue; it's pretty much physically impossible. Nonetheless
it can seem frightening.

If you are in the position of trying to assist someone in this
situation, open the person's mouth, tilt their head back slightly,
and grasp and hold their tongue out of the way of their airway
until they feel better. Avoid putting anything in their mouth;
this could easily fall in and make things much worse.

DXM can occasionally dry out your sinuses (an anticholinergic effect), so
check first to see if your nosebleed is a result of nasal irritation.
If so, treat it like you'd treat any other nosebleed.

If in doubt, or if you notice a prolonged nosebleed, burst capillaries in
the eyes or face, headache, or a sudden impairment of mental or motor
skills (hard to determine on DXM, I know), get medical help.
I'm not familiar with any cases of DXM-induced hypertensive CVAs,
although it might be possible, especially when mixed with stimulants
or MAOIs.

A suggestion was made to me from a physician that I'm going to pass along.
If you're going to be doing any sort of recreational
drugs which carry a risk of hypertension, you may wish to purchase a
sphygmomanometer (that blood pressure measuring gadget). They aren't
terribly expensive, and they can warn you when you're starting to get into
dangerous territory.

Remember, DXM at high levels can be very dissociative. You're
not dead, you just can't feel your body right now. This state
can have a lot in common with certain lucid dream states. A feeling
of "being dead" is common with third and fourth plateau
DXM doses. The best thing seems to be to try to make contact
with some part of your body (this can take a lot of effort), to
reassure you that you're still there. Then, relax and enjoy your
trip.

This is another reason why you should have a sober person with you.
If you are in any real danger, he or she should take care of
you.

Hangovers can occur from higher doses. Usually you can expect
to feel very relaxed if not lethargic for the next day after a
heavy trip. You may also might experience dizziness, muscle rigidity,
loss of balance, slight double-vision, and a general feeling of
being "not all there". Again, it goes away. Sleep
seems to improve things a great deal. Make sure to drink a lot
of liquids, get plenty of rest, take a multivitamin, and exercise.
As DXM is metabolized differently in different people, some may
experience hangovers (and trips) a lot longer than others; some have
had three-day trips and week-long hangovers. For more details, see
Section 6.1.7.

Very rarely, someone will come out of a DXM trip and seem to be
very dissociated from the real world, behaving a little like a
robot. Whenever this has been reported to me, the person in question
had always taken a high (third to fourth plateau) dose, and in
most cases had tried to achieve an out-of-body state (draw your
own conclusions). Make sure the person is relaxed, and try to
engage him or her in a familiar activity. Familiar environmental
cues should go a long way towards bringing him or her back to
the "real world". Also keep in mind that the person
may be slow to metabolize DXM and thus still be tripping.

If, after a couple of days, the person still hasn't returned to
normal, it's time to get worried. Contact your nearest psychologist,
priest, shaman, or other equivalent. Note that I don't think there's
any biological reason for this to happen.

Some papers on PCP have suggested that PCP can cause transient psychotic
breaks in susceptible individuals which can last up to ten days.
Hospitalization is recommended for the safety both of the patient and of
others. I've never heard of anything like this with DXM but it could
happen. This problem seems to resolve itself with or without psychiatric
intervention. After returning to normal, the person may not remember the
trip or a few days after it (355).

It's not generally a good idea to diagnose yourself, and I'm hesitant
to list in this section a diagnosis rather than symptoms. On the other
hand, serotonin syndrome is, at least at the time I'm writing this,
relatively unknown and probably underreported. And with increasing numbers
of people taking SSRIs like ProzacTM, the potential for serotonin syndrome
among users of DXM is rising.

The symptoms of serotonin syndrome are specified above (see
Section 6.2.9). Keep in mind that generally speaking anyone
on DXM will experience some of those symptoms, so don't freak out. The
point is, if you start noticing said symptoms when you aren't on DXM, or
if they are considerably stronger than usual, you might have a problem.

Don't panic. Serotonin syndrome is rarely fatal; usually it's just an
indication that you need to stop taking so many serotonergic drugs. There
are specific treatments for it (antiserotonergic drugs, appropriately enough),
and most of the symptoms respond adequately to benzodiazepines.

First off, let me distinguish between a bad trip and a true psychotic
break. Here's an example. If you feel like your ego is dissolving into a
puddle of jelly and you're suddenly confronted with frightening memories and
images, that's a bad trip. If you believe the aliens have implanted a homing
beacon in your brain and you have to drill a hole in your skull to let it out,
that's a psychotic break. Generally speaking if you're having a bad trip,
you still know you're on drugs. If you have a psychotic break, you probably
don't.

The most important thing, and it seems trivial, is to remember that it's
all in your mind. Your own mind is generating your experiences, and nothing
in there can truly harm you. Make sure you are in a quiet, calm place,
with limited sensory stimuli. If you find yourself having severe Lilliputian
hallucinations (i.e., everything seems the wrong size, either too big or
too small, or both), keep your eyes open and focus on a familiar object
that will give you a size reference.

If things seem to be getting worse, consider a light sedative, such
as as beer or two. Clinically, benzodiazepines have shown great utility in
terminating dissociative trips, but I do not recommend using them
except under the guidance of a physician. If you do use them, prepare to
slam into a "psychic wall" since the experience of suddenly stopping the
trip can be unpleasant, to say the least. Incidentally, by "psychic" I
mean the effects of psychedelics on the psyche (mind and consciousness),
not anything paranormal or spiritual.

Finally, try to keep a sense of humor about the whole thing. You aren't
generally in any danger from DXM (unless you've taken way too much, in
which case you should get yourself to the hospital), and it will end.

This section is probably of no use to you if you're the one experiencing
the psychotic break, and is primarily intended for trip-sitters. First
verify that the tripper is actually out of his gourd and not just playing
games (incidentally, this is a good reason to use a "safeword" when
tripping; when the safeword is spoken, take everything seriously until
further notice). Delusions on DXM, especially upper plateaus, are common
and not usually something to worry about since people aren't usually
motivated to act upon them.

If you've got a real problem on your hands, call the hospital and explain
the situation. Again, since DXM isn't a commonly known drug, you can tell
them it's similar to ketamine and PCP (an oversimplification, I know).
Be very careful in trying to restrain the tripper, since she or he may
perceive this as a threat, and will probably be mostly immune to pain.
Unless you can safely restrain someone (and unless you've had
training in this sort of thing, you probably can't), the tripper, like a
cornered animal, could beat the living shit out of you without thinking
twice.

Instead of restraint, try talking him or her down.
Be calm, soothing, and repeatedly remind the tripper that they have taken
a drug which has critically impaired their perceptions. Remind them of
who they are and how they got here, and that the experience will end.

I always try to keep a sense of humor in life ... after all, it's only a
temporary stop between incarnations anyhow. In view of that, I offer
some suggestions from readers on how to know when to stop.

You can identify a dozen different brands of cough syrup ... by
the smell alone

The local pharmacist starts asking about your tuberculosis problem

The checkout clerk calls you "that Robitussin junkie"

When you take out your recycling it's all brown glass bottles

You ran out of excuses at the supermarket and now just tell people
you like that cherry taste

If Drixoral Dollars were real you'd own a Ferrari

You haven't slept in two weeks, haven't eaten solid food in days,
and you've just told your parents that you're marrying an alien
from the desert planet Zolgar

You've gotten so used to your eyes moving independently that you
think you're actually a cleverly disguised lizard

You just made your fifth Christmas ornament out of those little
plastic shotglasses

People ask you why you're walking around in shorts and a T-shirt
sweating like a horse ... in the dead of winter.

Your native language now consists of grunts and bizarre gestures

Sophia Loren, Sean Connery, etc., come knocking at your door
offering a night of passion and you tell them you aren't into
"meat pleasures"

You think you're on the Internet ... physically.

You're sure you're actually a Jedi Master, but for some reason
your Jedi Mind Powers don't seem to work on the cop that just
arrested you for walking naked down Main Street.

On a more serious note, if you do start finding reality breaking down,
your friends avoiding you, or your grades or work performance dropping,
it's time to stop. DXM may be a lot of fun, but it just isn't worth
losing something truly important over.